Among dominant neurodegenerative disorders, Huntington's disease (HD) is perhaps the best candidate for treatment with small interfering RNAs (siRNAs) (Xia et al., 2002, 2004, 2006; Machida et al., 2006; Wang et al., 2005; Harper et al., 2005; DiFiglia et al., 2007; Ralph et al., 2005; Raoul et al., 2005). Invariably fatal, HD is caused by expansion of a CAG repeat in the Huntingtin gene, creating an extended polyglutamine tract that makes the Huntingtin protein toxic (The Huntington's disease collaborative research group, 1993). Silencing mutant Huntingtin messenger RNA (mRNA) should provide therapeutic benefit, but normal Huntingtin likely contributes to neuronal function (Auerbach et al., 2001, Cattaneo, et al., 2005; Dragatsis et al., 2000). No siRNA strategy can yet distinguish among the normal and disease Huntingtin alleles and other mRNAs containing CAG repeats (Caplen et al., 2002). siRNAs targeting the disease isoform of a heterozygous single-nucleotide polymorphism (SNP) in Huntingtin provide an alternative (Schwarz et al., 2006; Ding et al., 2003; Dahlgren et al., 2008; Du et al., 2005; Miller et al., 2004).